Elevated serum soluble endoglin (sCD105) decreased during extracorporeal elimination therapy for familial hypercholesterolemia.
ABSTRACT Extracorporeal elimination is a method of LDL-lowering therapy that is used in severe familial hypercholesterolemia (FH) after other therapeutic approaches have failed. There are currently no universally accepted biomarkers that would allow determining necessary intensity of therapy and frequency of future therapeutic interventions. An ideal tool for immediate evaluation would be a readily measurable serum marker. We hypothesized that soluble endoglin (sCD105), a recently described indicator of endothelial dysfunction, may represent such a tool. Eleven patients with FH (three homozygous, eight heterozygous; Fredrickson type IIa, IIb) that have been monitored for 4.5+/-2.8 years were treated; eight by LDL-apheresis and three by hemorheopheresis. 40 sCD105 measurements were done, before and after two consecutive elimination procedures. Baseline serum sCD105 levels were significantly higher in the patients (5.74+/-1.47 microg/l in series I, 6.85+/-1.85 microg/l in series II) than in the control group (3.85+/-1.25 microg/l). They decreased to normal after LDL-elimination (p=0.0003) in all except for one patient. This return to normal was not due to a non-specific capture of endoglin in adsorption or filtration columns as demonstrated by measurement of sCD105 before and after passage through the elimination media. We conclude that the soluble endoglin levels in patients with severe FH remain elevated despite long-term intensive therapy and that they decrease after extracorporeal elimination. Endoglin can therefore serve as a marker for evaluation of the treatment efficacy and of the decreased atherosclerotic activity in patients with FH treated by extracorporeal LDL-cholesterol elimination.
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ABSTRACT: Endoglin, also known as cluster of differentiation CD105, was originally identified 25 years ago as a novel marker of endothelial cells. Later it was shown that endoglin is also expressed in pro-fibrogenic cells including mesangial cells, cardiac and scleroderma fibroblasts, and hepatic stellate cells. It is an integral membrane-bound disulfide-linked 180 kDa homodimeric receptor that acts as a transforming growth factor-β (TGF-β) auxiliary co-receptor. In humans, several hundreds of mutations of the endoglin gene are known that give rise to an autosomal dominant bleeding disorder that is characterized by localized angiodysplasia and arteriovenous malformation. This disease is termed hereditary hemorrhagic telangiectasia type I and induces various vascular lesions, mainly on the face, lips, hands and gastrointestinal mucosa. Two variants of endoglin (i.e., S- and L-endoglin) are formed by alternative splicing that distinguishes from each other in the length of their cytoplasmic tails. Moreover, a soluble form of endoglin, i.e., sol-Eng, is shedded by the matrix metalloprotease-14 that cleaves within the extracellular juxtamembrane region. Endoglin interacts with the TGF-β signaling receptors and influences Smad-dependent and -independent effects. Recent work has demonstrated that endoglin is a crucial mediator during liver fibrogenesis that critically controls the activity of the different Smad branches. In the present review, we summarize the present knowledge of endoglin expression and function, its involvement in fibrogenic Smad signaling, current models to investigate endoglin function, and the diagnostic value of endoglin in liver disease.World journal of biological chemistry. 05/2014; 5(2):180-203.
- Current Opinion in Pharmacology 03/2013; · 5.44 Impact Factor
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ABSTRACT: Background. Rheohemapheresis (RHF) is a method that can stop the activity of the dry form of age-related macular degeneration (AMD). The pathophysiologic mechanisms are not well understood, and the effects of the RHF procedures extend beyond the time of the individual procedures. Patients and Methods. We present the data for 46 patients with AMD treated with a series of 8 rheohemapheretic procedures. Blood count parameters were measured before the first and the last procedures. The clinical effect was judged by changes in the drusenoid pigment epithelium detachment (DPED) area before and after the rheopheretic sessions. Results. Rheopheresis caused a decrease in hemoglobin (P < 0.001), a decrease in leukocytes (P < 0.034), and an increase in platelets (P < 0.005). We found a negative correlation between the amount of platelets and their volume (P < 0.001, Pearson correlation coefficient: -0.509). We identified the platelet/MPV ratio as a good predictor of the clinical outcome. Patients with a platelet/MPV ratio greater than 21.5 (before the last rheopheresis) had a significantly better outcome (P = 0.003, sensitivity of 76.9% and specificity of 80%). Conclusion. Several basic blood count parameters after RHF can be concluded to significantly change, with some of those changes correlating with the clinical results (reduction of the DPED area).BioMed research international. 01/2013; 2013:858219.